JP7522478B2 - Supercritical/subcritical fluid device, solvent extraction separation method, and product manufacturing method - Google Patents

Description

The present invention relates to a supercritical/subcritical fluid device, a solvent extraction separation method using the same, and a method for manufacturing products.

In recent years, the use of naturally derived functional ingredients has been attracting attention due to people's increasing health consciousness and interest in safety. These ingredients have been attracting attention for their use in maintaining and promoting health in fields from food to medicine, and in particular, their use in food-related fields such as supplements, health foods and beverages has been attracting even more attention. Furthermore, in fields such as cosmetics and general and medical drugs, naturally derived functional ingredients are attracting attention as key materials for increasing the added value of products.

In the manufacturing processes of pharmaceutical and food ingredients related to these naturally derived functional components, large amounts of organic solvents, which have a high environmental impact, may be used to dissolve the target substances.
On the other hand, since some organic solvents have adverse effects on the human body, the Ministry of Health, Labor and Welfare (Japan) has established guidelines for residual solvents in pharmaceutical manufacturing, which are widely known (see Internet URL: HTTPS://WWW.pmda.go.jp/files/000156502.pdf).

At present, it is unclear whether side effects or other problems caused by residual solvents occur in patients or users who orally or transdermally ingest, over the long term, medicines, supplements, foods, etc. manufactured under the above-mentioned regulations. In addition, similar regulations exist in the manufacturing process of food additives, etc., but as long as organic solvents are used to dissolve the target substances, problems related to residual solvents such as those mentioned above cannot be avoided.

Under the above background, the present inventors have been actively researching human- and environmentally-friendly solvent extraction and separation technology using only substances that exist in large quantities in nature, such as water, ethanol, and carbon dioxide (CO ₂ ), as a technology for producing safe and secure pharmaceutical and food materials. In the following Non-Patent Document 1, the present inventors have proposed a method that makes high use of the properties of the above substances, namely, water is highly polar, ethanol is amphipathic, and CO ₂ functions as a low-polarity solvent comparable to n-hexane under high pressure. Non-Patent Document 1 discloses a countercurrent-type supercritical fluid device that extracts and separates a solvent, recovering gas (gas phase) from the top of an extraction and separation column and a separated product (liquid phase: including the target substance) from the bottom, and providing an automatic back pressure valve at each of the two outlets for the gas phase and the liquid phase in the extraction and separation column. According to the supercritical fluid apparatus disclosed in Non-Patent Document 1, the above-mentioned configuration makes it possible to control the time interval between the open state and the closed state of each back pressure valve, so that extraction and separation of the solvent can be performed efficiently and reliably without any problems occurring in the continuous transfer of the gas and liquid phases once separated.

In addition, Non-Patent Document 2 proposes setting a lower limit on the extraction time from an extraction vessel in a parallel flow fluid device in order to prevent the vessel from being damaged by rapid depressurization of the vessel.

Patent Document 1 also proposes a countercurrent contactor for concentrating alcohol using supercritical fluids, in which raw material is fed from a fermentation alcohol supply line and a dissolving agent is fed from a dissolving agent supply line, and these are brought into contact in a countercurrent manner. The countercurrent contactor of Patent Document 1 is configured to extract alcohol from an upper line for extracting light liquids such as alcohol, and water from a lower line for extracting heavy liquids such as water, and is configured to extract alcohol and the like into an impurity separation tank and perform phase separation by opening a pressure reducing valve installed in the upper line to reduce pressure.

Patent Document 2 also proposes a system for recovering uranium and other metal-containing materials. In the system described in Patent Document 2, metal-containing materials containing a supercritical fluid solvent and the like are placed in a first station and a second station, and an extraction agent is introduced into the second station and then into the first station 18 to extract the metal. The extract is then moved to a stripping column, and the gas components are moved to a separator and reduced pressure, after which they are separated into gas and complexing agent.

Japanese Unexamined Patent Publication No. 62-25985 Special Publication No. 2008-533442

Y. Hoshino et al., ‘Fractionation of hops-extract-ethanol solutions using dense CO2 with a counter-current extraction column’, The Journal of Supercritical Fluids 136(2018), 37-43 E.A. Richter et al., ‘Thermodynamic properties of CO2 during controlled decompression of supercritical extraction vessels’, J. of Supercritical Fluids 98(2015), 102-110

As described above, when a sample containing a target component required in a manufacturing process using a supercritical fluid solvent or the like is separated into a gas phase using a fluid device equipped with a countercurrent column to obtain a target substance on the liquid phase side, the pretreatment of the sample generally tends to take a long time. In addition, depending on the pretreatment method, organic solvent may remain or some components may be reduced or denatured. For example, in a method for extracting and separating functional components from natural products, a pretreatment process is generally required in which a solid natural product sample is (1) dried, (2) crushed, and (3) extracted with an organic solvent. For this reason, the present inventors tried to determine whether a more rapid extraction process could be performed under conditions without taking a long time for pretreatment, without losing the target component, and without using an organic solvent, by directly converting the natural product raw material into a hydrothermal paste sample. However, the sample obtained by the hydrothermal paste method contains a slurry, and when such a sample is used in a manufacturing process using a supercritical fluid, the following problems arise.
In a manufacturing process using a supercritical fluid, the supercritical fluid undergoes adiabatic expansion at the outlet side of the back pressure valve, which is prone to freezing due to a drop in temperature. For this reason, when a slurry is pumped through a fluid device, the slurry containing solids at the outlet side of the back pressure valve may freeze, causing blockage in this area. In this case, for example, a heater may be installed on the outlet side of the back pressure valve to heat it. However, the discharge system using the interlocking back pressure valve described in Non-Patent Document 1 has a problem of being prone to blockage because it uses a solenoid-type back pressure valve with a fast opening and closing speed in addition to a thin tube of 1/16 inch.

As described above, when conventional fluidic devices are used to extract a slurry-like separated product, the back pressure valve on the liquid phase side can become clogged, forcing the process to be stopped and frequent maintenance work to be performed. This can lead to reduced productivity and increased time and costs required for maintenance.

The present invention has been made in consideration of the above problems, and aims to provide a supercritical/subcritical fluid device that is excellent in productivity and maintainability, and a solvent extraction separation method and product manufacturing method using the same, without causing blockages in back pressure valves or piping, even when a slurry-like separated product is extracted from the liquid phase side.

The present inventors have conducted further intensive research to solve the above problems. As a result, they have found that by optimizing the configuration and opening/closing conditions of the back pressure valve and adopting a configuration that generates a pressure difference between the gas phase side and the liquid phase side of the separation and extraction column, it is possible to suppress the occurrence of sudden adiabatic expansion at the outlet side of the back pressure valve and prevent the slurry-like separated material from freezing and causing blockage. Furthermore, they have found that by generating a pressure difference between the gas phase side and the liquid phase side, it is easy to take out the separated material (target substance) containing the slurry from the discharge port on the liquid phase side located at the bottom of the separation and extraction column, and have completed the present invention.
That is, the present invention has the following aspects.

A separation and extraction column, a first liquid delivery section connected to the bottom of the separation and extraction column via a first flow path and supplying a mobile phase that becomes a supercritical fluid, a second liquid delivery section connected to the top of the separation and extraction column via a second flow path and supplying a substance to be separated, a first back pressure adjustment mechanism connected to the bottom of the separation and extraction column via a third flow path and setting the inside of the separation and extraction column to a first pressurized state that keeps the mobile phase in a supercritical fluid state, and a fourth back pressure adjustment mechanism connected to the top of the separation and extraction column via a fourth flow path and setting the inside of the separation and extraction column to a first pressurized state that keeps the mobile phase in a supercritical fluid state. A supercritical/subcritical fluid device, a solvent extraction separation method using the supercritical/subcritical fluid device, and a method for producing a product containing a target substance obtained using the supercritical/subcritical fluid device as a functional ingredient, the device comprising: a second back pressure adjustment mechanism that sets the second pressurized state to a pressure that maintains the pressure in a stable state; and a control unit that controls the first back pressure adjustment mechanism and the second back pressure adjustment mechanism, the control unit controlling the first back pressure adjustment mechanism and the second back pressure adjustment mechanism so as to reduce the second pressurized state by a predetermined pressure difference with respect to the first pressurized state.

According to the supercritical/subcritical fluid device of the present invention, as described above, the control unit controls the first back pressure adjustment mechanism and the second back pressure adjustment mechanism so as to reduce the second pressurized state by a predetermined pressure difference with respect to the first pressurized state. This generates a pressure difference between the gas phase side and the liquid phase side of the separation and extraction column, suppressing the occurrence of sudden adiabatic expansion at the outlet side of the first back pressure adjustment mechanism and preventing the slurry separated product from freezing and causing blockage. In addition, the pressure difference between the gas phase side and the liquid phase side makes it easier to remove the slurry separated product from the liquid phase side located at the bottom of the separation and extraction column.
Therefore, it is possible to provide a supercritical/subcritical fluid device with excellent productivity and maintainability.

In addition, the solvent extraction separation method according to the present invention employs a method in which the supercritical/subcritical fluid apparatus according to the present invention having the above-mentioned configuration is used to bring the mobile phase, which is a supercritical fluid, into countercurrent contact with the object to be separated in a separation and extraction column, and the solvent is extracted and separated from the object to be separated, thereby separating and recovering the target substance from the object to be separated. As a result, as in the above, it is possible to prevent the slurry-like separated product from freezing and causing blockages on the outlet side of the first back pressure adjustment mechanism, and it is easy to remove the slurry-like separated product from the liquid phase side.
Therefore, it becomes possible to continuously separate and recover the target substance from the object of separation with good productivity.

In addition, according to the method for producing a product according to the present invention, the supercritical/subcritical fluid device according to the present invention having the above-mentioned configuration is used to produce a product containing the target substance obtained as a functional component, so that similarly, it is possible to prevent the slurry-like separated product from freezing and causing blockages on the outlet side of the first back pressure adjustment mechanism, and it is easy to remove the slurry-like separated product from the liquid phase side.

FIG. 1 is a schematic diagram for explaining a supercritical/subcritical fluid apparatus, a solvent extraction separation method, and a product manufacturing method according to one embodiment of the present invention, and is a system diagram showing an example of a supercritical fluid apparatus.

Hereinafter, one embodiment of the supercritical/subcritical fluid apparatus, solvent extraction separation method, and product manufacturing method according to the present invention will be described with reference to FIG.
In addition, in each drawing used in the following description, for the sake of convenience, characteristic parts may be shown enlarged in order to make the features easier to understand, and the dimensional ratios may differ from the actual ones. Furthermore, the materials, dimensions, etc. exemplified in the following description are merely examples, and the present invention is not limited thereto, and can be appropriately changed and implemented within the scope that does not change the gist of the present invention.

<Supercritical fluid device>
The overall configuration of the supercritical/subcritical fluid apparatus of this embodiment will be described in detail below with reference to FIG.
FIG. 1 is a system diagram showing in outline the overall configuration of a supercritical/subcritical fluid device 100 according to the present embodiment.
In the present invention, "supercritical" refers to a state in which the properties of a liquid (dissolving power) and the properties of a gas (diffusion power) are combined at a predetermined temperature and a predetermined high pressure. On the other hand, "subcritical" refers to a state at a temperature and pressure slightly lower than the critical point of supercriticality. The present invention uses a normal supercritical fluid to concentrate the target object, but as will be described in detail later, the pressure of the device is partially reduced, so that the subcritical state is partially included in the treatment process, and therefore, strictly speaking, it is a supercritical/subcritical fluid device. For this reason, in the following description, "supercritical/subcritical fluid device" is abbreviated to "supercritical fluid device", but this includes the scope of the supercritical fluid device including the subcritical state under reduced pressure in the present invention.

As shown in FIG. 1, the supercritical fluid device 100 of this embodiment is generally configured to include a separation and extraction column 30, a first liquid delivery section 10, a second liquid delivery section 20, a first back pressure adjustment mechanism 40, a second back pressure adjustment mechanism 50, and a control section (not shown) that controls the supercritical fluid device 100.
As will be described in detail later, the supercritical fluid device 100 of this embodiment controls the first back pressure adjustment mechanism 40 and the second back pressure adjustment mechanism 50 by a control unit (not shown) so as to lower the second pressurized state of the separation and extraction column 30 adjusted by the second back pressure adjustment mechanism 50 by a predetermined pressure difference relative to the first pressurized state of the separation and extraction column 30 adjusted by the first back pressure adjustment mechanism 40. More specifically, in the supercritical fluid device 100, the lower side (the lower end 30a side in FIG. 1 ) of the separation and extraction column 30 is in the above-mentioned first pressurized state, and the upper side (the upper end 30b side in the same figure) is in the second pressurized state.

The first liquid delivery section 10 is connected to the lower inlet 31 of the separation and extraction column 30 via the first flow path 11, and supplies a mobile phase that becomes a supercritical fluid. In one example described in this embodiment, it supplies a supercritical fluid C to the lower part of the separation and extraction column 30. The first liquid delivery section 10 in the illustrated example has a supercritical fluid source storage tank 1, a pressure reducing valve 2, a filter 3, a liquid delivery pressure pump 4, a cooling machine 5, a safety valve 6, a flow rate control valve 7, and a vent valve 8.

The supercritical fluid source storage tank 1 stores therein a fluid source that will become a supercritical fluid, and the upper outlet 1a is connected to the first flow path 11, so that the fluid source is supplied to the separation and extraction column 30 via this first flow path 11. The supercritical fluid source storage tank 1 is not particularly limited, and any metal tank that is commonly used in this field can be used without any restrictions. In this embodiment, an example is described in which carbon dioxide is used as the gas or liquid that will become the supercritical fluid, but organic carbon such as water, ethanol, and glycerin can be used in addition to carbon dioxide.

The pressure reducing valve 2 is provided in the first flow path 11 near the outlet 1a of the supercritical fluid source storage tank 1, and controls the fluid source derived from the supercritical fluid source storage tank 1 to a constant pressure. There are no particular limitations on the pressure reducing valve 2, and for example, a pressure reducing valve of a general configuration that is connected to a high-pressure tank can be used without any limitations.

The filter 3 is provided in the first flow path 11 downstream of the pressure reducing valve 2 in the flow direction of the fluid source, and removes impurities contained in the fluid source. There are no particular limitations on the filter 3, and a filter of a general configuration used in fluid purification processing can be used.

The liquid pressure delivery pump 4 may be, for example, an HPLC pump (high performance liquid chromatography pump). The liquid pressure delivery pump 4 is provided downstream of the filter 3 in the flow direction of the supercritical fluid C in the first flow path 11, and pressurizes the fluid source contained in the supercritical fluid source storage tank 1 via the first flow path 11 to deliver the liquid. The liquid pressure delivery pump 4 is not limited to an HPLC pump, and may be a general plunger pump used for pressurizing and pumping fluids.

The cooling machine 5 is used to cool the fluid source flowing through the first flow path 11 when it is adiabatically compressed, and in the illustrated example, is provided alongside the liquid delivery pressure pump 4. The liquefied fluid source is pressurized and pumped by the liquid delivery pressure pump 4 to become a supercritical fluid C. As such a cooling device, for example, one that uses general water or a refrigerant can be used without any restrictions.

The safety valve 6 can be opened in an emergency, for example, if some malfunction occurs in the flow of the supercritical fluid C in the first flow path 11. There are no particular limitations on the type of safety valve 6, and it is possible to adopt a valve that is commonly used in this field.

The flow control valve 7 appropriately adjusts the amount of supercritical fluid C supplied to the separation and extraction column 30. There are no particular limitations on the type of flow control valve 7, and it is possible to use a general valve used to control the flow rate of fluids.

The vent valve 8 is provided to discharge air and excess liquid, for example, when performing maintenance on the supercritical fluid device 100. There are no particular limitations on the vent valve 8, and any valve commonly used in this field can be used without any restrictions.

The first liquid delivery section 10 having the above configuration delivers the supercritical fluid C from the supercritical fluid source storage tank 1 to the separation and extraction column 30 through the first flow path 11 by the liquid delivery pressure pump 4 equipped with a cooling device 5, and then through the lower inlet 31 of the separation and extraction column 30, the details of which will be described later.

The second liquid delivery section 20 is connected to the top of the separation and extraction column 30 via a second flow path 21 and supplies the material to be separated. In one example described in this embodiment, a feed solution B containing a raw material (a sample containing a slurry in this embodiment) and a modifier (a co-solvent or entrainer, ethanol or an aqueous ethanol solution in this embodiment) is supplied to the top of the separation and extraction column 30. The second liquid delivery section 20 in the illustrated example has a storage tank 22 for the material to be separated, a liquid delivery pressure pump 23, and a flow control valve 24.

The separation subject solution storage tank 22 stores therein the raw material, which is the separation subject containing the target substance M, and the feed solution B, which is composed of a modifier, and one end of the second flow path 21 is inserted into the opening 22a on the upper end side, so that the feed solution B is supplied to the separation and extraction column 30 via this second flow path 21. The separation subject solution storage tank 22 is not particularly limited, and metal tanks, glass containers, and the like that are commonly used in this field can be used without any restrictions.

The liquid delivery pressure pump 23 is disposed on the outlet side of the separation object solution storage tank 22 in the path of the second flow path 21, and delivers the feed solution B consisting of the raw material and modifier contained in the separation object solution storage tank 22 via the second flow path 21. There are no particular limitations on the liquid delivery pressure pump 23, and any pump commonly used for pressurizing and pumping fluids can be used without any restrictions.

The flow control valve 24 appropriately adjusts the amount of feed solution B supplied to the separation and extraction column 30. There are no particular limitations on the flow control valve 24, and it is possible to use a general valve used to control the flow rate of a fluid, similar to the flow control valve 7 described above.

In the separation and extraction column 30, a supercritical fluid C, which is a mobile phase that becomes a supercritical fluid, is introduced from a lower inlet 31, and a feed solution B, which is a separation target containing a target substance M, is introduced from an upper inlet 32. In this way, the separation and extraction column 30 constitutes a so-called countercurrent column in which the supercritical fluid C and the feed solution B come into contact with each other in a countercurrent direction inside the separation and extraction column 30.
In the illustrated example, the separation and extraction column 30 is disposed inside an oven 70, with its lower side (lower end 30a side) disposed inside a first oven 70A and its upper side (upper end 30b side) disposed inside a second oven 70B.

The separation and extraction column 30 is one containing packing such as Dixon packing, which is commonly used in supercritical extraction applications. In the separation and extraction column 30, the above-mentioned packing causes countercurrent contact between the supercritical fluid C and the feed solution B, which is made up of a raw material containing raw material components and ethanol and water, and the components, which are the target substance M contained in the raw material, are distributed between the gas phase and the liquid phase, so that the components are concentrated and extracted from the lower end 30a and the upper end 30b.

The separation and extraction column 30 outputs a liquid phase extract from the lower end 30a shown in FIG. 1 toward a first back pressure adjustment mechanism 40, which will be described later, and outputs a gas phase extract from the upper end 30b toward a second back pressure adjustment mechanism 50, which will be described later.

As described above, the oven 70 has a first oven 70A at the bottom and a second oven 70B at the top. The first oven 70A and the second oven 70B are each configured to be capable of heating the internal space in which the separation and extraction column 30 is housed by a heater or the like (not shown).

A pre-ribbon heater 71 is provided inside first oven 70A and is attached to first flow path 11 for pre-heating fluid C in a supercritical state flowing through first flow path 11.
A pre-ribbon heater 72 is provided inside the second oven 70B, and is attached to the second flow path 21 to pre-heat the feed solution B flowing through the second flow path 21.

In addition, inside the first oven 70A, downstream of the pre-ribbon heater 71 arranged in the path of the first flow path 11 in the flow direction of the supercritical fluid C, a pressure sensor P is provided to detect the pressure upstream of the separation and extraction column 30.

The supercritical fluid C flowing through the first flow path 11 is preheated to a predetermined temperature by a pre-ribbon heater 71 disposed inside the first oven 70A, and is supplied into the separation and extraction column 30 from the lower inlet 31 while being heated as a supercritical fluid by the first oven 70A.

In this embodiment, for example, a raw material containing a target substance M derived from a natural product and a feed solution B consisting of ethanol and water are supplied from the separation target solution storage tank 22 to the top of the separation and extraction column 30 by a liquid pressure feed pump 23. Such feed solution B is preheated to a predetermined temperature by a pre-ribbon heater 72, and is supplied into the separation and extraction column 30 from the top inlet 32 while being heated by the second oven 70B.

The first back pressure adjustment mechanism 40 is a back pressure valve that is connected to the lower end (lower part) 30a of the separation and extraction column 30 via a third flow path 41 and adjusts the inside of the separation and extraction column 30 to a first pressurized state that keeps the mobile phase in a supercritical fluid state. As the first back pressure adjustment mechanism 40, a spring-type mechanical valve is preferable as a back pressure valve whose opening degree can be finely changed as needed, but a commonly used solenoid valve or the like can be used as long as the opening degree can be adjusted.

Furthermore, the diameter of the flow passage piping of the third flow passage 41 may be changed so as to be thicker (the cross-sectional area is increased) before and after the first back pressure adjustment mechanism 40 .
For example, a piping of 1/16 inch (about 1.6 mm) size is generally used upstream of the first back pressure adjustment mechanism 40, but in the case of a sample containing a slurry, if the same size piping is used downstream of the first back pressure adjustment mechanism 40, clogging will often occur. Therefore, if a pipe with a larger inner diameter is used downstream of the first back pressure adjustment mechanism 40, for example, a pipe with a 1/4 inch (about 6.3 mm) size that is four times the size of the upstream pipe, clogging is less likely to occur even when a sample containing a slurry is used.
Since adiabatic expansion is highly likely to occur before and after the first back pressure adjustment mechanism 40, by changing the inner diameter of the piping at the positions before and after the occurrence of adiabatic expansion, clogging of the piping can be prevented.
The first back pressure adjustment mechanism 40 may be provided with a heater to prevent freezing.

The first separation tank 42 is disposed downstream of the first back pressure adjustment mechanism 40 in the flow direction of the liquid phase extract discharged from the lower end 30a of the separation and extraction column 30. The first separation tank 42 in the example shown in Figure 1 is configured as a multi-stage tank consisting of an upstream tank 42a and a downstream tank 42b.
The first separation tank 42 separates the liquid phase extract that is discharged from the lower end 30a of the separation and extraction column 30 and reduced in pressure by the first back pressure adjustment mechanism 40 into, for example, a slurry containing a concentrate of the target substance M and the other slurry, and separates and recovers the concentrate of the target substance M.
In addition, the fluid (carbon dioxide gas) G separated at this time can be recovered from the wet gas flow meter 43 arranged in the downstream stage and reused.

The second back pressure adjustment mechanism 50 is a back pressure valve that is connected to the upper end (upper portion) 30b of the separation and extraction column 30 via a fourth flow path 51 and adjusts the inside of the separation and extraction column 30 to a second pressurized state that maintains the mobile phase in a supercritical fluid state. In the illustrated example, the second back pressure adjustment mechanism 50 is connected to the upper end 30b of the separation and extraction column 30 via an outlet valve 54 provided in the fourth flow path 51. As with the first back pressure adjustment mechanism 40, a general solenoid valve or the like that can finely change the opening degree can be used as the second back pressure adjustment mechanism 50.
The second back pressure adjustment mechanism 50 may be provided with a heater to prevent freezing.
Since the second back pressure adjustment mechanism 50 side contains almost no slurry, there is no risk of clogging. However, like the upstream and downstream of the first back pressure adjustment mechanism 40, the piping of the fourth flow path 51 may be configured to have a large diameter.

The second separation tank 52 is disposed downstream of the second back pressure adjustment mechanism 50 in the flow direction of the gas-phase extract emerging from the upper end 30b of the separation and extraction column 30. Like the first separation tank 42, the second separation tank 52 in the example shown in Figure 1 is also configured as a multi-stage tank comprising a front-stage tank 52a and a rear-stage tank 52b.
The second separation tank 52 separates the gas-phase extract that is discharged from the upper end 30b of the separation and extraction column 30 and depressurized by the second back pressure adjustment mechanism 50 into, for example, an aqueous ethanol solution that was a modifier and a fluid (carbon dioxide gas) G. The fluid (carbon dioxide gas) G separated at this time can also be recovered from a dry gas flow meter 53 in the downstream stage and reused.

A wet gas flow meter 43 is provided on the outlet side of the first separation tank 42, i.e., downstream of the flow direction of the liquid phase extract. The wet gas flow meter 43 can detect the flow rate of the fluid (carbon dioxide gas) G separated in the first separation tank 42 in real time, and can also monitor the operating status of the supercritical fluid device 100 in real time.

A dry gas flow meter 53 is provided on the outlet side of the second separation tank 52, i.e., downstream of the flow direction of the gas phase extract. The dry gas flow meter 53 can detect the flow rate of the fluid (carbon dioxide gas) G separated by the supercritical fluid device 100 in real time, and can also monitor the operating status of the supercritical fluid device 100 in real time, as described above.

The control unit, which is not shown in FIG. 1, controls the entire supercritical fluid device 100, including the first back pressure adjustment mechanism 40 and the second back pressure adjustment mechanism 50, and in this embodiment, controls the first back pressure adjustment mechanism 40 and the second back pressure adjustment mechanism 50 in a linked manner.
The control unit provided in the supercritical fluid device 100 of this embodiment controls the first back-pressure adjustment mechanism 40 and the second back-pressure adjustment mechanism 50 so as to reduce the second pressurized state maintained by the second back-pressure adjustment mechanism 50 by a predetermined pressure difference relative to the first pressurized state maintained by the first back-pressure adjustment mechanism 40 in the separation and extraction column 30.

A control unit (not shown) appropriately controls the opening degrees of the first back pressure adjustment mechanism 40 and the second back pressure adjustment mechanism 50 based on the detection value (pressure) of a pressure sensor P arranged upstream of the separation and extraction column 30, as well as the detection values of a wet gas flow meter 43 and a dry gas flow meter 53 respectively provided downstream in the flow direction of each fluid in the separation and extraction column 30.
The supercritical fluid device 100 of the present embodiment is provided with a control unit that controls the first back pressure adjustment mechanism 40 and the second back pressure adjustment mechanism 50, thereby making it possible to appropriately adjust the pressurized state within the separation and extraction column 30, as described above.

The pressures of the first pressurized state and the second pressurized state, which are maintained by the control unit controlling the first back pressure adjustment mechanism 40 and the second back pressure adjustment mechanism 50, are not particularly limited as long as the second pressurized state is lower by a predetermined pressure difference and is a pressure that can maintain the fluid C in a supercritical state in a supercritical fluid state.

On the other hand, in this embodiment, particularly when the feed solution B contains the target substance (separated product) M in a slurried form in the raw material, from the viewpoint of preventing the separated product from freezing, it is preferable that the second pressurized state is at a lower pressure in the range of 0.05 MPa to 0.15 MPa than the first pressurized state described above. In other words, it is preferable that the control unit controls the first back pressure adjustment mechanism 40 and the second back pressure adjustment mechanism 50 so that the second pressurized state is at a lower pressure in the range of 0.05 MPa to 0.15 MPa than the first pressurized state in the separation and extraction column 30.

Specifically, the method for realizing the above pressure state is as follows: first, the second back pressure adjustment mechanism 50 is opened (at this time, the first back pressure adjustment mechanism 40 is closed), and the flow rate of the liquid delivery pump 4 and the opening degree and opening time (first specified time) of the second back pressure adjustment mechanism 50 are adjusted so that the dry gas flow meter 53 indicates a constant flow rate, thereby extracting a portion of the supercritical fluid and reducing the pressure of the second pressurized state (step (i)).
Next, the second back pressure adjustment mechanism 50 is closed and the first back pressure adjustment mechanism 40 is opened, and the flow rate of the wet gas flow meter 43, the flow rate of the liquid delivery pump 23, the aperture and the aperture time (second predetermined time) of the first back pressure adjustment mechanism 40 are adjusted to extract a portion of the supercritical fluid (step (ii)).
Then, the second back pressure adjustment mechanism 50 is opened and the first back pressure adjustment mechanism 40 is closed again, and the above steps (i) and (ii) are repeated at predetermined intervals to control the amount of each extraction by adjusting the opening degree. When this operation results in a low pressure difference between the first pressurized state and the second pressurized state in the range of 0.05 MPa to 0.15 MPa (hereinafter sometimes referred to as the "steady state"), the first separation tank 42 is installed and a concentrate of the target substance M is separated and recovered (step (iii)).

In the present invention, the steady state is reached by performing multiple withdrawals as described above in order to confirm whether the steady state has been reached while preventing changes in the characteristics of the supercritical fluid due to sudden pressure changes and malfunctions of the separation and extraction column 30. Whether the steady state has been reached is determined by checking whether the detection value of the pressure sensor P and the discharge during withdrawal are steady (whether there are no disturbed pulsations (intervals) and the ejection of the extracted material is stable (whether it is ejected uniformly from the flow path)).

The above-mentioned control may be performed, for example, while observing and photographing the state of the internal fluid under high pressure in real time through a viewing window provided in the oven 70.
When the flow rates are adjusted as described above, the flow rates may be determined from a phase diagram of a component system based on a PR (Pegn-Robinson) model for a vapor-liquid equilibrium state.

The control unit controls the first back pressure adjustment mechanism 40 and the second back pressure adjustment mechanism 50 so that the pressures in the first pressurized state and the second pressurized state are in a steady state relationship, thereby generating a pressure difference between the gas phase side (upper end 30b side) and the liquid phase side (lower end 30a side) in the separation and extraction column 30. This suppresses the occurrence of sudden adiabatic expansion at the outlet side of the first back pressure adjustment mechanism 40, thereby suppressing freezing of the slurry-like separated product. This prevents blockages in the first back pressure adjustment mechanism 40 and the piping before and after it, resulting in excellent productivity of the target substance M and excellent maintainability.
Furthermore, by generating a pressure difference between the gas phase side and the liquid phase side of the separation and extraction column 30 as described above, a force is generated by the pressure difference to push the slurry-like separated concentrate from the lower part of the separation and extraction column 30, i.e., the lower end 30a located on the liquid phase side, making it easier to remove the separated concentrate.

In addition, it is preferable that the control unit opens the second back pressure adjustment mechanism 50 to set the second pressurized state at the upper side of the separation and extraction column 30 to a lower pressure with a predetermined pressure difference relative to the first pressurized state at the lower side, and then closes the second back pressure adjustment mechanism 50 and opens the first back pressure adjustment mechanism 40. By controlling the opening and closing timing of the first back pressure adjustment mechanism 40 and the second back pressure adjustment mechanism 50 as described above, when collecting a slurry-like concentrate (separated product) of the target substance M contained in the feed solution B, it is possible to prevent blockages in the first back pressure adjustment mechanism 40 and piping due to freezing of the separated product.

When implementing the above-mentioned control, it is preferable to appropriately adjust and set the opening/closing timing and opening degree between the first back pressure adjustment mechanism 40 and the second back pressure adjustment mechanism 50 so as to prevent backflow, etc., occurring before or after each of the back pressure valves that constitute these mechanisms or within the separation and extraction column 30.

The control unit can continuously perform the operation of the supercritical fluid device 100 in a steady state and the operation of repeatedly controlling the opening and closing of the first back pressure adjustment mechanism 40 and the second back pressure adjustment mechanism 50 described above. This makes it possible to obtain the target substance M while maintaining the excellent operating efficiency of the supercritical fluid device 100. From the viewpoint of the operating efficiency of such a supercritical fluid device 100, it is preferable that the difference in opening and closing timing between the first back pressure adjustment mechanism 40 and the second back pressure adjustment mechanism 50 is as small as possible. On the other hand, if the difference in opening and closing timing is too small, there is a possibility that each fluid will be drawn out simultaneously from the liquid phase side and the gas phase side of the separation and extraction column 30. For this reason, it is preferable that the control unit appropriately adjusts and sets the above-mentioned difference in opening and closing timing to be equal to or greater than a certain level.

The opening time (and closing time) of the first back pressure adjustment mechanism 40 and the second back pressure adjustment mechanism 50 are not particularly limited, but it is preferable to set the opening time (and closing time) of the first back pressure adjustment mechanism 40 to about 2 to 3 seconds, for example, in the control unit, taking into account the opening and closing timing described above.

The control unit (not shown) is not particularly limited, and for example, a dedicated circuit consisting of a control circuit equipped with a CPU or the like can be used. Alternatively, for example, by connecting a general personal computer (PC) or tablet terminal to the supercritical fluid device 100, the PC or tablet terminal can be used as the control unit.

In addition, although not shown in FIG. 1, the supercritical fluid device 100 of this embodiment may further include an evaporator or the like that separates the target substance M from the ethanol solution (ethanol aqueous solution) when the concentrated extract (target substance M) contains a modifier (e.g., an ethanol solution or an ethanol aqueous solution).
Furthermore, as described above, when the fluid (e.g., carbon dioxide gas) separated in the first separation tank 42 or the second separation tank 52 is recovered and reused, a configuration may be adopted that includes a circulation mechanism (not shown) for reliquefying the fluid and returning it to the supercritical fluid source storage tank 1 for recirculation.

The object to be separated by the supercritical fluid device 100 of this embodiment is not particularly limited, and it is possible to separate and extract objects containing various substances, but the above-mentioned excellent effects can be achieved particularly when performing a separation process for an object to be separated that contains a target substance in a sample that contains a solid matter in a slurry state as described above.

<Solvent extraction separation method>
The solvent extraction separation method of this embodiment will be described below with reference to the configuration of the supercritical fluid apparatus 100 of this embodiment shown in Fig. 1. Note that detailed description of the configuration of the supercritical fluid apparatus 100 already described will be omitted.

The solvent extraction separation method of this embodiment uses the supercritical fluid device 100 of this embodiment to bring supercritical state fluid C, which is a mobile phase that becomes a supercritical fluid, into countercurrent contact with feed solution B containing the substance to be separated in a separation and extraction column 30, and extracts and separates the solvent from feed solution B, thereby separating and recovering concentrated target substance M from feed solution B.

According to the solvent extraction separation method of this embodiment, the supercritical fluid device 100 of this embodiment is used to separate and recover the concentrated target substance M from the feed solution B, which prevents the slurry-like separated product from freezing and causing blockage at the outlet side of the first back pressure adjustment mechanism 40 connected to the lower end 30a of the separation and extraction column 30, as described above. In addition, the use of the supercritical fluid device 100 makes it easier to extract the concentrated target substance M from the lower end 30a, which is the liquid phase side of the separation and extraction column 30. Therefore, it is possible to continuously separate and recover the concentrated target substance M from the feed solution B with good productivity.

<Product manufacturing method>
The method for producing a product of this embodiment is similar to the solvent extraction separation method of this embodiment described above, in that it uses the supercritical fluid apparatus 100 of this embodiment shown in FIG. 1 to concentrate and separate a target substance M from a separation subject (e.g., a feed solution B containing a raw material and a modifier), and produces a product containing the concentrated and separated target substance M as a functional component.

The specific process in the manufacturing method of the product of this embodiment is the same as the solvent extraction separation method of this embodiment described above, and a detailed description thereof will be omitted.

<Target substance separated and extracted from the separation target>
Target substances that can be obtained by the supercritical fluid apparatus of the present embodiment as described above and the solvent extraction separation method using the same are not particularly limited, but examples thereof include various foods, medicines, supplements, etc.

As described above, the supercritical fluid device and solvent extraction separation method of this embodiment can suppress freezing of the separated product (target substance) from a slurry sample, prevent internal blockages, and facilitate extraction of a concentrated product of the target substance M. Therefore, the target substances obtained by the supercritical fluid device and solvent extraction separation method of this embodiment, i.e., foods, medicines, supplements, etc., are highly productive, and are of high quality because no organic solvents or unnecessary pretreatment are required.

The supercritical fluid device and solvent extraction separation method of this embodiment are useful not only for productivity and quality based on the above-mentioned industrial production perspective, but also for the development of various applications, such as the production of medicines that are friendly to people and the global environment, and the separation of colors, aromas, and flavors in the production of foods and beverages.

<Action and effect>
As described above, according to the supercritical fluid apparatus of the present embodiment, as described above, the control unit (not shown) controls the first back pressure adjustment mechanism 40 and the second back pressure adjustment mechanism 50 so as to reduce the second pressurized state at the upper side by a predetermined pressure difference with respect to the first pressurized state at the lower side in the separation and extraction column 30. As a result, a pressure difference occurs between the gas phase side and the liquid phase side in the separation and extraction column 30, so that the occurrence of sudden adiabatic expansion at the outlet side of the first back pressure adjustment mechanism 40 can be suppressed, and the slurry-like separated product can be prevented from freezing and causing blockage. In addition, the occurrence of a pressure difference between the gas phase side and the liquid phase side makes it easy to take out the separated product from the lower end 30a, which is the liquid phase side of the separation and extraction column 30. Therefore, a supercritical fluid apparatus 100 with excellent productivity and maintainability can be provided.

In addition, according to the solvent extraction separation method of this embodiment, a method is adopted in which the target substance M is separated and recovered from the feed solution B containing the object to be separated using the supercritical fluid device 100 having the above-mentioned configuration. As a result, as in the above, it is possible to prevent the slurry-like separated product from freezing and causing blockage at the outlet side of the first back pressure adjustment mechanism 40, and it is also possible to easily remove the slurry-like separated product from the liquid phase side. Therefore, it is possible to continuously separate and recover the target substance M from the feed solution B containing the raw material with good productivity.

<Other aspects of the present invention>
Although the preferred embodiments of the present invention have been described in detail above, the present invention is not limited to the specific embodiments described above, and various modifications and changes are possible within the scope of the gist of the present invention described in the claims.

The supercritical fluid apparatus of the present invention is excellent in productivity and maintainability, without causing blockages in back pressure valves or piping, even when a slurry-like separated product is extracted from the liquid phase side. Since the apparatus can handle a slurry-like separated product, the labor and time required for pretreatment when extracting a target substance from naturally occurring components is reduced, and since the target substance is less likely to denature and does not contain harmful organic solvents, products with excellent productivity and safety can be applied. Therefore, the supercritical fluid apparatus of the present invention is highly suitable for the manufacturing process of products that use the target substance obtained using the supercritical fluid apparatus of the present invention and contain the target substance as a functional ingredient, such as pharmaceuticals, cosmetics, supplements, and food ingredients.

100...Supercritical/subcritical fluid device (supercritical fluid device)
LIST OF SYMBOLS 10: First liquid delivery section 11: First flow path 1: Supercritical fluid source storage tank 2: Pressure reducing valve 3: Filter 4: Liquid delivery pressure pump 5: Cooling machine 6: Safety valve 7: Flow rate control valve 8: Vent valve 20: Second liquid delivery section 21: Second flow path 22: Separation target solution storage tank 22a: Opening 23: Liquid delivery pressure pump 24: Flow rate control valve 30: Separation and extraction column 30a: Lower end (lower side)
30b...(upper side)
31: Lower inlet 32: Upper inlet 40: First back pressure adjustment mechanism 41: Third flow path 42: First separation tank 42a: Pre-stage tank 42b: Post-stage tank 43: Wet gas flow meter 50: Second back pressure adjustment mechanism 51: Fourth flow path 52: Second separation tank 52a: Pre-stage tank 52b: Post-stage tank 53: Dry gas flow meter 54: Outlet valve 60: Control unit 70: Oven 70A: First oven 70B: Second oven 71, 72: Pre-ribbon heater P: Pressure sensor C: Supercritical fluid (mobile phase that becomes a supercritical fluid)
B: Feed solution containing raw material and modifier (subject to be separated)
M: Target substance (slurry-like target substance; separated product)
G...Fluid (carbon dioxide gas)

Claims (8)

A separation and extraction column;
a first liquid delivery section connected to a lower portion of the separation and extraction column via a first flow path and configured to supply a mobile phase that becomes a supercritical fluid;
a second liquid delivery section connected to an upper portion of the separation and extraction column via a second flow path and supplying a material to be separated;
a first back pressure adjustment mechanism connected to a lower portion of the separation and extraction column via a third flow path, and configured to set the inside of the separation and extraction column to a first pressurized state for maintaining the mobile phase in a supercritical fluid state;
a second back pressure adjustment mechanism connected to an upper portion of the separation and extraction column via a fourth flow path, and configured to set the inside of the separation and extraction column to a second pressurized state for maintaining the mobile phase in a supercritical fluid state;
A control unit that controls the first back pressure adjustment mechanism and the second back pressure adjustment mechanism,
the control unit controls the first back pressure adjustment mechanism and the second back pressure adjustment mechanism so as to reduce the second pressurized state by a predetermined pressure difference with respect to the first pressurized state. The supercritical/subcritical fluid device according to claim 1, characterized in that the cross-sectional area of the third flow path downstream of the first back pressure adjustment mechanism is larger than the cross-sectional area of the flow path connected to the separation/extraction column side of the first back pressure adjustment mechanism. The supercritical/subcritical fluid device according to claim 1 or 2, characterized in that the control unit controls the first back pressure adjustment mechanism and the second back pressure adjustment mechanism so that the second pressurized state is a pressure in the range of 0.05 MPa to 0.15 MPa lower than the first pressurized state. The control unit is
(i) in a state where the first back pressure adjustment mechanism is closed, the second back pressure adjustment mechanism is opened for a first predetermined time to extract a first predetermined amount of fluid, thereby reducing the second pressurized state relative to the first pressurized state;
(ii) closing the second back pressure adjustment mechanism and opening the first back pressure adjustment mechanism for a second predetermined time to extract a second predetermined amount of fluid;
(iii) The supercritical/subcritical fluid device according to claim 1 or 2, characterized in that the operations of (i) and (ii) are repeated to control the second pressurized state to a lower pressure with respect to the first pressurized state at the predetermined pressure difference. The supercritical/subcritical fluid device according to claim 1 or 2, characterized in that the object to be separated contains a target substance in a slurry state. The supercritical/subcritical fluid device according to claim 5, characterized in that the control unit further performs control to close the second back pressure adjustment mechanism and open the first back pressure adjustment mechanism to collect an extract containing the slurry-like target substance contained in the separation object. A solvent extraction and separation method using the supercritical/subcritical fluid device according to claim 1 or 2, in which the mobile phase which becomes the supercritical fluid is brought into countercurrent contact with the separation target in the separation and extraction column, and the solvent is extracted and separated from the separation target, thereby separating and recovering a target substance from the separation target. 3. A method for producing a product comprising concentrating and separating a target substance from a separation subject using the supercritical/subcritical fluid apparatus according to claim 1 or 2, and containing the concentrated and separated target substance as a functional component.

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